Clinical MRI studies correlate decreases in molecular diffusion to abnormal regions within brain tissue. As a result, diffusion weighed MRI is exquisitely sensitive to brain pathologies such as stroke. The aim of this proposal is to elucidate determinants of molecular diffusion in the extracellular space of brain and to clarify the factors important for comparing diffusion measurements derived from different experimental techniques. The two primary methods that generate diffusion measurements in brain tissue are iontophoresis and magnetic resonance (MR) spectroscopy. Although both methods have been extensively used by multiple research groups to generate quantitative measurements in normal brain and in many pathological brain states, comparisons between the two bodies of research are complicated by the unknown effects of differences in the experimental methodologies. This proposal outlines a strategy for calibrating the two methods. The fundamental experimental involves measuring diffusion of the same molecule with both techniques. After initial comparisons are made, the MR diffusion measurements will be altered so that they are sensitive to motions over a mean distance that approaches the distance between the electrodes used for the iontophoresis measurements. Finally, the change in the observed diffusion rates will be assessed under ischemic conditions to assess the degree to which both diffusion measurements respond to the same anatomical changes at the onset of ischemia.